..We are now equipped with powerful genetic models that continue to uncover new aspects of the pathogenesis of Huntington disease and will be instrumental for the development of therapeutic approaches for this disease...

BIOMEDICINE: One Misfolded Protein Allows Others to Sneak By

Gillian P BatesKing s College London School of Medicine, London SE1 9RT, UKScience 311:1385-6. 2006

John S BettKing s College London School of Medicine, Department of Medical and Molecular Genetics, King s College London, London, United KingdomJ Cell Mol Med 13:2645-57. 2009

..These results suggest that the expression of aggregation-prone mutant htt causes disturbances to the ubiquitin system, which may contribute to disease due to the diverse and important roles of ubiquitin...

Formation of polyglutamine inclusions in a wide range of non-CNS tissues in the HdhQ150 knock-in mouse model of Huntington's disease

Hilary MoffittDepartment of Medical and Molecular Genetics, King s College London School of Medicine, London, United KingdomPLoS ONE 4:e8025. 2009

..At the maximum tolerated dose, we achieved steady-state riluzole levels of 100 microM in brain. However, this was insufficient to inhibit aggregation in vivo and we found no improvement in the disease phenotype...

..RNA-targeted therapeutic strategies designed to lower the levels of HTT are under development. Many of these approaches would not prevent the production of exon 1 HTT and should be reviewed in light of our findings...

Michal MielcarekDepartment of Medical and Molecular Genetics, King s College London, London, United KingdomPLoS ONE 6:e27746. 2011

..We found that SAHA reduces SDS-insoluble aggregate load in the cortex and brain stem but not in the hippocampus of the R6/2 brains, and that this was accompanied by restoration of Bdnf cortical transcript levels...

Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington's disease

..Here, we discuss the potential therapeutic pathways through which histone deacetylase inhibitors might act to correct the aberrant transcription observed in Huntington's disease and other polyglutamine repeat diseases...

HDAC4 does not act as a protein deacetylase in the postnatal murine brain in vivo

Michal MielcarekDepartment of Medical and Molecular Genetics, King s College London, London, United KingdomPLoS ONE 8:e80849. 2013

..The lack of a major effect on the transcriptional profile is consistent with the cytoplasmic location of HDAC4 in the P3 murine brain. ..

Genetic knock-down of HDAC3 does not modify disease-related phenotypes in a mouse model of Huntington's disease

Lara MoumnéDepartment of Medical and Molecular Genetics, King s College London, London, United KingdomPLoS ONE 7:e31080. 2012

..We conclude that HDAC3 should not be considered as the major mediator of the beneficial effect induced by SAHA and other HDAC inhibitors in HD...

Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of Huntington's disease

Ivan RattrayKing s College London, Institute of Psychiatry, Department of Neuroscience, London, United Kingdom King s College London, Department of Medical and Molecular Genetics, London, United KingdomPLoS ONE 8:e84726. 2013

..In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear. ..

..Mouse models have proved extremely useful in these goals and are now also being used for the preclinical testing of therapeutic compounds. This chapter reviews the successes and limitations of the approaches that have been developed...

..Our results indicate that a decrease in mRNA levels underlie the depletion of protein levels of rabphilin 3A, and we suggest that this reduction may be involved in causing impaired synaptic transmission in R6/1 mice...

Alterations in the mouse and human proteome caused by Huntington's disease

..Maintaining alpha1-antitrypsin and alphaB-crystallin availability during the course of Huntington's disease might prevent neuronal cell death and therefore could be useful in delaying the disease progression...

..Proteins of interest were evaluated using immunoblotting and ELISA in plasma from 2 populations, CSF and R6/2 mice. The identified proteins demonstrate neuroinflammation in HD and warrant further investigation as possible biomarkers...